715 research outputs found
A New Possibility of Dynamical Study on Solid State Ionic Materials by Inelastic Neutron Scattering
A new technique of inelastic neutron scattering measurement utilizing the multiple incident energies is applied to the dynamical study of vitreous silica. A wide variety of extracted information from a series of two-dimensional maps of dynamical structure factor with multiple different incident energies are greatly valuable. The applicability and its expected contribution of new experimental technique into the further progress of scientific activities in solid state ionic materials are discussed.Received: 30 September 2010; Revised: 25 October 2010; Accepted: 26 October 201
A novel mechanism of actin filament processive capping by formin: solution of the rotation paradox
The FH2 domains of formin family proteins act as processive cappers of actin filaments. Previously suggested stair-stepping mechanisms of processive capping imply that a formin cap rotates persistently in one direction with respect to the filament. This challenges the formin-mediated mechanism of intracellular cable formation. We suggest a novel scenario of processive capping that is driven by developing and relaxing torsion elastic stresses. Based on the recently discovered crystal structure of an FH2–actin complex, we propose a second mode of processive capping—the screw mode. Within the screw mode, the formin dimer rotates with respect to the actin filament in the direction opposite to that generated by the stair-stepping mode so that a combination of the two modes prevents persistent torsion strain accumulation. We determine an optimal regime of processive capping, whose essence is a periodic switch between the stair-stepping and screw modes. In this regime, elastic energy does not exceed feasible values, and supercoiling of actin filaments is prevented
ICER is requisite for Th17 differentiation.
Inducible cAMP early repressor (ICER) has been described as a transcriptional repressor isoform of the cAMP response element modulator (CREM). Here we report that ICER is predominantly expressed in Th17 cells through the IL-6-STAT3 pathway and binds to the Il17a promoter, where it facilitates the accumulation of the canonical enhancer RORγt. In vitro differentiation from naive ICER/CREM-deficient CD4(+) T cells to Th17 cells is impaired but can be rescued by forced overexpression of ICER. Consistent with a role of Th17 cells in autoimmune and inflammatory diseases, ICER/CREM-deficient B6.lpr mice are protected from developing autoimmunity. Similarly, both anti-glomerular basement membrane-induced glomerulonephritis and experimental encephalomyelitis are attenuated in ICER/CREM-deficient mice compared with their ICER/CREM-sufficient littermates. Importantly, we find ICER overexpressed in CD4(+) T cells from patients with systemic lupus erythematosus. Collectively, our findings identify a unique role for ICER, which affects both organ-specific and systemic autoimmunity in a Th17-dependent manner
Polymer flooding – Does Microscopic Displacement Efficiency Matter?
Polymer flooding is an enhanced oil recovery (EOR) technique that aims to enhance the stability of the flood front in order to increase sweep efficiency and thereby increase hydrocarbon recovery. Polymer flooding studies often focus on large-scale sweep efficiency and neglect the impact of the pore-scale displacement efficiency of the multi-phase flow. This work explores the pore-scale behavior of water vs polymer flooding, and examines the impact of rock surface wettability on the microscopic displacement efficiency using digital rock physics. In this study, a micro-CT image of a sandstone rock sample was numerically simulated for both water and polymer flooding under oil-wet and water-wet conditions. All simulations were performed at a capillary number of 1E-5, corresponding to a capillary dominated flow regime. Results of the four two-phase flow imbibition simulations are analyzed with respect to displacement character, water phase break-through, viscous/capillary fingering, and trapped oil. In the water-wet scenario, differences between water flood and polymer flood are small, with the flood front giving a piston-like displacement and breakthrough occurring at about 0.4 pore volume (PV) for both types of injected fluid. On the other hand, for the oil-wet scenario, water flood and polymer flood show significant differences. In the water flood, fingering occurs and much of the oil is bypassed early on, whereas the polymer flood displaces more oil and thereby provides better microscopic sweep efficiency throughout the flood and especially around breakthrough. Overall the results for this rock sample indicate that water flood and polymer flood provide similar recovery for a water-wet condition, while the reduced mobility ratio of polymer flood gives significantly improved recovery for an oil-wet condition by avoiding the onset of microscopic (pore-scale) fingering that occurs in the water flood. This study suggests that depending on the rock-fluid conditions, the use of polymer can impact microscopic sweep efficiency, in addition to the well-known effect on macroscopic sweep behavior.La inyección de polímeros es una técnica de recobro mejorado de petróleo (EOR) que tiene como objetivo mejorar la estabilidad del frente de inyección para aumentar la eficiencia del desplazamiento de hidrocarburos y, por lo tanto, incrementar el factor de recobro. Lo estudios de inyección de polímeros a menudo se centran en la eficiencia del desplazamiento a gran escala e ignoran el impacto de los mecanismos de desplazamiento a escala microscópica, y rara vez evalúan la variabilidad de parámetros de flujo multifásico en el medio poroso. Este trabajo explora el comportamiento del agua contra la inyección de polímeros en el medio poroso, y examina el impacto de la humectabilidad de la superficie de la roca en la eficiencia de desplazamiento microscópico, utilizando tomografía computarizada de rayos X en muestras de roca. En este estudio, se simuló numéricamente una imagen de microtomografía computarizada de una muestra de roca arenisca, para un proceso de inyección de agua y polímeros en condiciones de mojabilidad al aceite y al agua. Todas las simulaciones se realizaron a un número capilar de 1E-5, correspondiente a un régimen de flujo dominado por fuerzas capilares y que es típico del flujo en yacimientos de hidrocarburos. Los resultados de las cuatro simulaciones de imbibición de flujo de dos fases se analizan con respecto al carácter desplazante, el avance de la fase acuosa, la digitación viscosa y capilar, y el aceite atrapado. En el escenario de mojabilidad al agua, las diferencias entre la inyección de agua y la inyección de polímeros son pequeñas, dado que el frente de inyección produce un
desplazamiento en forma de pistón y un avance que se produce a aproximadamente 0,4 volúmenes porosos para ambos tipos de fluido inyectado. Por otro lado, para el escenario de mojabilidad al petróleo, la inyección de agua y la inyección de polímeros muestran diferencias significativas. En la inyección de agua, se produce digitación y gran parte del petróleo se pasa por alto al principio; mientras que la inyección de polímeros desplaza más aceite y, por lo tanto, proporciona una mejor eficiencia de desplazamiento microscópico durante la inyección, especialmente alrededor de la ruptura. En general, los resultados para esta muestra de roca indican que la inyección de agua y la inyección de polímeros proporcionan un efecto de recobro similar para una condición de mojabilidad al agua, mientras que la relación de movilidad reducida de la inyección de polímeros proporciona un efecto de recobro significativamente mejorado para una condición de mojabilidad al aceite, al evitar la aparición de digitación microscópica (a escala de poro) que se produce en la inyección de agua. Este estudio sugiere que, dependiendo de las condiciones roca-fluido, el uso del polímero puede impactar la eficiencia de desplazamiento microscópico, además del efecto conocido sobre el comportamiento del desplazamiento macroscópico
Surface-Emitted Green Light Generated In Langmuir-Blodgett-Film Wave-Guides
We demonstrate second-harmonic generation due to counterpropagating beams in planar waveguides of 2-docosylamino-5-nitropyridine (DCANP). The DCANP molecules were deposited by Langmuir-Blodgett techniques and have a preferred alignment within the substrate plane. Four-layer waveguide structures were used to optimize the trade-off between propagation loss and efficient surface-emitted green light
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Implementation of earlier antibiotic administration in patients with severe sepsis and septic shock in Japan: a descriptive analysis of a prospective observational study.
BACKGROUND: Time to antibiotic administration is a key element in sepsis care; however, it is difficult to implement sepsis care bundles. Additionally, sepsis is different from other emergent conditions including acute coronary syndrome, stroke, or trauma. We aimed to describe the association between time to antibiotic administration and outcomes in patients with severe sepsis and septic shock in Japan. METHODS: This prospective observational study enrolled 1184 adult patients diagnosed with severe sepsis based on the Sepsis-2 criteria and admitted to 59 intensive care units (ICUs) in Japan between January 1, 2016, and March 31, 2017, as the sepsis cohort of the Focused Outcomes Research in Emergency Care in Acute Respiratory Distress Syndrome, Sepsis and Trauma (FORECAST) study. We compared the characteristics and in-hospital mortality of patients administered with antibiotics at varying durations after sepsis recognition, i.e., 0-60, 61-120, 121-180, 181-240, 241-360, and 361-1440 min, and estimated the impact of antibiotic timing on risk-adjusted in-hospital mortality using the generalized estimating equation model (GEE) with an exchangeable, within-group correlation matrix, with "hospital" as the grouping variable. RESULTS: Data from 1124 patients in 54 hospitals were used for analyses. Of these, 30.5% and 73.9% received antibiotics within 1 h and 3 h, respectively. Overall, the median time to antibiotic administration was 102 min [interquartile range (IQR), 55-189]. Compared with patients diagnosed in the emergency department [90 min (IQR, 48-164 min)], time to antibiotic administration was shortest in patients diagnosed in ICUs [60 min (39-180 min)] and longest in patients transferred from wards [120 min (62-226)]. Overall crude mortality was 23.4%, where patients in the 0-60 min group had the highest mortality (28.0%) and a risk-adjusted mortality rate [28.7% (95% CI 23.3-34.1%)], whereas those in the 61-120 min group had the lowest mortality (20.2%) and risk-adjusted mortality rates [21.6% (95% CI 16.5-26.6%)]. Differences in mortality were noted only between the 0-60 min and 61-120 min groups. CONCLUSIONS: We could not find any association between earlier antibiotic administration and reduction in in-hospital mortality in patients with severe sepsis
Crystal Structure of the Formin mDia1 in Autoinhibited Conformation
Formin proteins utilize a conserved formin homology 2 (FH2) domain to nucleate new actin filaments. In mammalian diaphanous-related formins (DRFs) the FH2 domain is inhibited through an unknown mechanism by intramolecular binding of the diaphanous autoinhibitory domain (DAD) and the diaphanous inhibitory domain (DID).Here we report the crystal structure of a complex between DID and FH2-DAD fragments of the mammalian DRF, mDia1 (mammalian diaphanous 1 also called Drf1 or p140mDia). The structure shows a tetrameric configuration (4 FH2 + 4 DID) in which the actin-binding sites on the FH2 domain are sterically occluded. However biochemical data suggest the full-length mDia1 is a dimer in solution (2 FH2 + 2 DID). Based on the crystal structure, we have generated possible dimer models and found that architectures of all of these models are incompatible with binding to actin filament but not to actin monomer. Furthermore, we show that the minimal functional monomeric unit in the FH2 domain, termed the bridge element, can be inhibited by isolated monomeric DID. NMR data on the bridge-DID system revealed that at least one of the two actin-binding sites on the bridge element is accessible to actin monomer in the inhibited state.Our findings suggest that autoinhibition in the native DRF dimer involves steric hindrance with the actin filament. Although the structure of a full-length DRF would be required for clarification of the presented models, our work here provides the first structural insights into the mechanism of the DRF autoinhibition
Rhodobacter capsulatus forms a compact crescent-shaped LH1–RC photocomplex
Rhodobacter (Rba.) capsulatus has been a favored model for studies of all aspects of bacterial photosynthesis. This purple phototroph contains PufX, a polypeptide crucial for dimerization of the light-harvesting 1–reaction center (LH1–RC) complex, but lacks protein-U, a U-shaped polypeptide in the LH1–RC of its close relative Rba. sphaeroides. Here we present a cryo-EM structure of the Rba. capsulatus LH1–RC purified by DEAE chromatography. The crescent-shaped LH1–RC exhibits a compact structure containing only 10 LH1 αβ-subunits. Four αβ-subunits corresponding to those adjacent to protein-U in Rba. sphaeroides were absent. PufX in Rba. capsulatus exhibits a unique conformation in its N-terminus that self-associates with amino acids in its own transmembrane domain and interacts with nearby polypeptides, preventing it from interacting with proteins in other complexes and forming dimeric structures. These features are discussed in relation to the minimal requirements for the formation of LH1–RC monomers and dimers, the spectroscopic behavior of both the LH1 and RC, and the bioenergetics of energy transfer from LH1 to the RC.journal articl
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